The first objective of this research project is to develop radiobiological test systems for the quantitative measurement of the toxicity of intracellularly deposited low-energy electrons and to use these systems to determine the radiotoxicity of radio nuclides commonly used in Nuclear Medicine. The radiotoxicity of iodine-125 as IUdR incorporated into DNA has been studied in cultured cell systems using clonal survival as end point. Other cellular damages including division delay, single-strand breaks in DNA, and cytogenetic aberrations will also be studied. We shall further explore the effects of other low- energy electron-emitting radionuclides (technetium-99m, selenium-75, gallium-67, chromium-51) in the test systems developed for iodine-125 studies. Our second objective in this project is to pursue the therapeutic implications of our observation that iodine-125 affixed to DNA is extremely radiotoxic. We plan to examine the extraction of 125IUdR by the first circuit through solid tumors, to measure the uptake in vitro and in vivo by an experimental ascites tumor, and to determine the dose- uptake-radiation response relationships in these tumors.